Potassium depletion stimulates mRNA expression of proximal tubule AT1 angiotensin II receptors.
Dietary potassium (K+) deficiency is associated with blood pressure elevation and impaired urinary sodium excretion. Since angiotensin II is a potent stimulator of tubular sodium transport, we studied the effect of low [K+] on expression of kidney AT1 angiotensin receptors. In rabbits fed a K+-deficient diet for 14 days, plasma [K+] was significantly reduced compared to rabbits fed a standard diet (control: 4.06 +/- 0.12 vs. K+-deficient: 2.66 +/- 0.19 mmol/l; p < 0.001; n = 6-9). By Northern hybridization or RNase protection assays, dietary K+ deficiency caused an increase in mRNA expression for AT1 receptors in kidney cortex (43.5 +/- 12.9% increase vs. control; p < 0.04; n = 8), and in proximal tubule segments in suspension (76.4 +/- 28.8% increase vs. control; p < 0.005; n = 6). K+ deficiency had no effect on AT1 receptor mRNA expression in liver, or on mRNA expression of beta-actin in kidney cortex, proximal tubule suspensions, or liver. To determine if low extracellular [K+] might directly modulate AT1 receptor mRNA expression, primary cultures of rabbit proximal tubule cells were incubated for 1, 3, 6 or 24 h in media with or without 5 mmol/l K+. Incubation of cells in 0 mmol/l K+ caused a 99.2 +/- 32.9% increase in AT1 receptor mRNA expression at 3 h (p < 0.001; n = 14), returning to control levels by 24 h. Incubation of proximal tubule cells in 0 mmol/l K+ also caused a significant increase in basolateral membrane specific binding of [125I]-angiotensin II (p < 0.05; n = 4). These results indicate that dietary K+ deficiency and low extracellular [K+] stimulate expression of kidney AT1 angiotensin II receptors. Increased AT1 receptor mRNA and protein expression in proximal tubule may promote enhanced sodium reabsorption in K+ deficiency.
Burns
K D
KD
Department of Medicine, University of Ottawa, and Ottawa General Hospital, Ont., Canada. kburns@ogh.on.ca
Smith
I B
IB
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004032:Diet; D005260:Female; D007457:Iodine Radioisotopes; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D011191:Potassium Deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000096:biosynthesis*; D012260:Ribonucleases / Q000378:metabolism
D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D012260:Ribonucleases